| アブストラクト | BACKGROUND: Vorasidenib is a dual inhibitor of isocitrate dehydrogenase-1 and isocitrate dehydrogenase-2 used to treat patients with grade 2 astrocytoma or oligodendroglioma with either mutation. Vorasidenib has yet to be linked to cases of acute liver injury. AIMS: We describe 3 cases of severe acute liver injury with features of autoimmune hepatitis associated with vorasidenib and summarize 50 cases of vorasidenib-associated liver injury reported to the FDA. METHODS: This was a case series of 3 patients who developed severe acute liver injury during vorasidenib treatment. A search of the FDA Adverse Event Reporting System database identified 50 cases of suspected drug-induced liver injury from vorasidenib with usable information. RESULTS: Onset of elevated alanine aminotransferase activities (ALT) were 13, 31, and 2 weeks after vorasidenib initiation. Pattern of liver injury was hepatocellular; mean ALT 1748 U/L, bilirubin level 69.4 mumol/L, and R value 63.9. Despite discontinuation of vorasidenib, ALT continued to increase, and with histology showing centrizonal confluent necrosis, prompted initiation of 40-60 mg prednisone for possible drug induced autoimmune-like hepatitis. ALT normalized and steroids were tapered over 23, 3, and 7 months respectively. Patients remained in remission for 7-25 months after discontinuation of steroids. Among FAERS cases, mean latency to > 3x upper limit of normal ALT was 66 days, 9 were hospitalized, 7 received steroids, and 6 cases with sufficient data met Hy's Law criteria. CONCLUSION: Data suggest that vorasidenib-induced liver injury is hepatocellular with a subset that presents with autoimmune-like features which responds to a finite course of corticosteroids. |
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| 投稿者 | Lau, Emily A; Braxton, David R; Autran, Didier; Chen, Fengming; Haffner, Aurelie M; Hu, Jethro; Peters, Katherine B; Fong, Tse-Ling |
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| 組織名 | Hoag Memorial Hospital Presbyterian, Hoag Digestive Health Institute, Newport;Beach, CA, USA.;Department of Pathology, Hoag Memorial Hospital Presbyterian, Newport Beach, CA,;USA.;Neuro-Oncology Department, AP-HM, University Hospital Timone, 13005, Marseille,;France.;Department of Pathology, Duke University, Durham, NC, USA.;Department of Pathology, AP-HM, Aix Marseille University, CHU Timone, Marseille,;Division of Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los;Angeles, CA, USA.;Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA.;Beach, CA, USA. tseling.fong@hoag.org.;Liver Program, Hoag Memorial Hospital Presbyterian, One Hoag Drive, Newport;Beach, CA, 92663, USA. tseling.fong@hoag.org. |
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